Gene therapies are approaches for making genes exhibit intrinsic functions by externally inducing normal genes in place of disease-causing genes, and are taken into consideration as methods for curing hereditary diseases and other diseases, such as cardiovascular diseases, immune diseases, endocrine diseases, or cancers. However, in order to achieve effective gene therapies, it is necessary to transfer genes into cells. To this end, research into methods for transmitting genes into cells is being conducted, including a method using a transmitter such as a viral or non-viral vector, a physical method, such as a micro glass capillary injection method, an ultrasonic method or an electroporation method.
In the method of using a transmitter such as a viral or non-viral vector, representative examples of the viral vector include retrovirus, adenovirus, lentivirus, and so on, which are known to be highly infective to have high gene delivery efficiency. However, when the viral vector is inserted into a host chromosome, it is limited in its usage because it causes mutation, creation of infective virus, a possibility of causing an inflammation in the host. Therefore, owing to simplicity or a relatively low risk, numerous studies of the method of using a non-viral vector, such as a cationic polymer, are being made. This method is reportedly advantageous in that genes can be stabilized by forming a complex through electrostatic interaction with negatively-charged genes and intracellular delivery of genes is facilitated by positive charges.
However, when the cationic polymer is used in an amount enough to obtain a sufficient effect, which still is, however, less sufficient than the viral transmitter, it may cause acute toxicity and may make it difficult to achieve transfer specific to a target cell. In addition, since the cationic polymer combines with various proteins in blood, its stability is severely deteriorated, so that it is different to be used in vivo.
Therefore, in order to compensate for the aforementioned shortcomings, a method for solving problems of toxicity and instability in blood has been researched by forming a tertiary complex of a gene/cationic polymer composite and an anionic polymer. However, the tertiary complex of a gene/cationic polymer composite and an anionic polymer considerably reduces gene delivery efficiency while being capable of lowering toxicity. In addition, the tertiary complex still has a technological difficulty in view of target cell specific transfer.
In addition, it has been reported that the non-viral gene transmitter vector and the gene composite are taken up via endocytosis. However, the gene/non-viral vector composite delivered to the endosome by the endocytosis may stay in the endosome to then be fused with lysosome, causing decomposition of the gene by various digestive enzymes present in the lysosome, thereby noticeably lowering the gene delivery efficiency. Therefore, the gene/non-viral vector composite delivered by the endocytosis may be separated from the endosome, so that the capability of the gene/non-viral vector composite moving to the cytoplasm serves as quite an important factor in increasing the gene delivery efficiency.
Meanwhile, photodynamic therapy (PDT) is a technology of treating lesions using a photosensitizer and an appropriate amount of light (photon) even without performing a surgical operation. A porphyrin-series compound, which is typically used as the photosensitizer, is extracted from silkworm powder, mulberry leaves, green algae or the like, has suitable spectroscopic characteristics and may cause electronic transition by green light (700-900 nm) having relatively large cell penetrating capability. When excited by light having a particular wavelength, the photosensitizer may create activated oxygen (e.g., singlet oxygen, oxygen radical, superoxide, peroxide, or the like). The created activated oxygen is involved in oxidation of lipid, protein and hexane and disruption of intracellular structures, resulting in apoptosis.
In addition, a porphyrin derivative as a photosensitizer material is deposited to be selectively to cancer cells. The deposition of the porphyrin derivative is presumably accounted for by receptors for low density lipoprotein (LDL) in charge of porphyrin transport, which are highly expressed in cancer cells. However, most of photosensitizers are insoluble and exhibit side effects in human body due to phototoxicity demonstrated by a long retention time. In addition, the photosensitizer based therapy requiring irradiation of an appropriate amount of light (photon) has a disadvantage in that it cannot be used for large-sized tumor cells due to a limitation in light delivery.
Therefore, in order to enhance therapeutic effects, two therapies of photodynamic therapy (PDT) and drug therapy using gene, anti-cancer medicine or protein drug may be combined, instead of singly performing the photodynamic therapy (PDT) or the drug therapy.
In the conventional therapy, the gene, anti-cancer medicine or protein drug gene is not delivered to a target portion at the same time with the photosensitizer but is subjected to photon irradiation a predetermined time after the photosensitizer is injected. In the conventional therapy, various kinds of drugs should be injected many times, and it is impossible to transfer the drugs specifically to the lesion portions. In addition, since the photosensitizer and the therapeutic drug are not formed in a single body, they may not be positioned on the same part in a cell.